Endocrine Disrupting Effects of Herbicides and Pentachlorophenol: In Vitro and in Vivo Evidence

Abstract

The potential for agricultural chemicals to cause endocrine disruption (ED) in humans and wildlife is an increasing concern; however, the effects of commonly used pesticides at environmentally relevant concentrations are largely unknown. Therefore, 12 environmentally relevant pesticides (11 herbicides and pentachlorophenol (PCP)) were tested for their endocrine disrupting potential in two in vitro assays. A recombinant yeast screen was used to detect receptor mediated (anti-) estrogenic and (anti-) androgenic activity (concentration range: 0.01-1000 microM), and cultured Xenopus oocytes were used to measure effects on the ovulatory response and ovarian steroidogenesis (concentration range: 0.00625-62.5 microM). Eleven pesticides were active in at least one assay (isoproturon, diuron, linuron, 4-chloro-2-methylphenoxy acetic acid (MCPA), mecoprop, atrazine, simazine, PCP, trifluralin, chlorpropham, bentazone), and one had no effect (2,4-dichlorophenoxy acetic acid (2,4,-D)). The most common effects were antiestrogenic/ antiandrogenic activity in the yeast screen, and inhibition of ovulation in vitro, accompanied by decreased testosterone production. Estrogenic activity was never observed. In addition, the most potent compound identified in vitro (PCP) was tested for ED activity in vivo. A short-term exposure (6 days) of adult female Xenopus to low concentrations (0.1 or 1 microg/L; 0.375 or 3.75 nM) resulted in minor alterations in plasma hormone levels and toxic effects on the ovary. Changes in in vitro human chorionic gonadotropin (hCG) stimulated hormone production in ovarian follicles from exposed individuals was also observed. In conclusion, novel effects of herbicides and PCP at environmentally relevant concentrations were found, and the effects of these compounds on humans and/or wildlife warrant further investigation.

Pentachlorophenol affected both reproductive and interrenal systems: In silico and in vivo evidence

“…with these steroid receptors were approximate equivalent. These results may provide molecular evidences for previously reported estrogenic, anti-estrogenic, anti-androgenic activity of PCP in vitro (Suzuki et al, 2001;Jung et al, 2004;Orton et al, 2009;Li et al, 2008aLi et al, , 2008bLi et al, , 2010b and in vivo (Zha et al, 2006;Zhang et al, 2008a). Moreover, molecular docking results showed that PCP could not interact with any of the agonistic or antagonistic conformations of CYPs.…”

“…PCP has been demonstrated to display estrogenic, anti-estrogenic, antiandrogenic, thyroid receptor and retinoid X receptor antagonistic activity in vitro (Suzuki et al, 2001;Jung et al, 2004;Orton et al, 2009;Li et al, 2008aLi et al, , 2008bLi et al, , 2010b and disturb the hypothalamic-pituitary-gonadal (HPG) axis in vivo (Zha et al, 2006;Zhang et al, 2008a). However, the underlying mechanism such as molecular initiating event (MIE) and the following regulating process has not been fully understood.…”

Widely Used Pesticides with Previously Unknown Endocrine Activity Revealed as in Vitro Antiandrogens

“…Furthermore, hormone receptor screening in vitro suggests a preponderance of anti androgenic activity compared with estrogenic activity in non organochlorine (currentuse) pesticides. For example, Kojima et al (2004) screened 161 pesticides and reported that 52 were anti androgenic, whereas only 29 were estrogenic, and Orton et al (2009) reported that 6 of 12 pesticides screened were anti androgenic and none were estrogenic. There is a good correlation between androgen receptor (AR) antagonist properties and in vivo anti androgenic effects, and there is also good evidence that androgen-sensitive end points are demasculinized in male rats when exposed in utero to a wide range of pesticides.…”

Endocrine Disrupting Compounds in Lotic Ecosystems: A Review on Its Occurrence, Sources and Effects on Chironomus riparius

“…Nowadays, PCP is a restricted use pesticide and is no longer available to the public due to its carcinogenic and endocrine disrupting effects [55,56]. Morales et al [40] studied the effect of PCP in the expression of heat-shock genes, concluding that, at a concentration of 1 µM, no significant effects were observed in the expression of HSP70 and HSC70.…”